Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
  • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
  • A61L2/08—Radiation
  • A61L2/087—Particle radiation, e.g. electron-beam, alpha or beta radiation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
  • A61L2202/10—Apparatus features
  • A61L2202/11—Apparatus for generating biocidal substances, e.g. vaporisers, UV lamps
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
  • A61L2202/20—Targets to be treated
  • A61L2202/23—Containers, e.g. vials, bottles, syringes, mail

Definitions

• the present invention refers to a method of steril- izing a container.
• Electron irradiation is a generally known sterilization method, and the mechanism behind the lethal effect has been thoroughly studied.
• the main lethal mech- anism of the irradiation is that these electrons within a cell break bonds in the DNA chain.
• a further problem is that the ozone formed in turn can react with the package material, and the reaction products obtained can give an off flavor when solubilized from the material.
• the ozone generated is considered to result in product limitations in that sensitive products are more difficult to pack.
• the purpose of the invention is to provide a method of the kind mentioned by way of introduction, which method allows a more effective sterilization of closed containers in a cheap and simple way, the problems mentioned above being eliminated.
• Fig. 1 shows the killing of microorganisms as a logarithmic reduction (LGR) after electron irradiation of sealed PET bottles containing air (empty rectangles) or helium (hatched rectangles) .
• LGR logarithmic reduction
• Ozone is known to be a strong oxidant of organic substances, but the prospects of using ozone has been limited by the high investment and operating costs for its production.
• ozone molecules - in the form of activated oxygen - by means of chain reaction give rise to what is called free radicals which result in that biomo- lecules (DNA, RNA, enzy ⁇ nic and structural proteins, and saturated fatty acids, etc.) are changed and destroyed.
• biomo- lecules DNA, RNA, enzy ⁇ nic and structural proteins, and saturated fatty acids, etc.
• enzymes in a cell can be influenced by the oxidative change of their catalytic or allo- steric centra.
• the air which has been activated by means of electron irradiation is according to the invention utilized in that the container is sealed before the electron irradiation is started and the ozone formed is retained within the closed container for the purpose of sterilizing the same.
• an environment rich in ozone is produced, which during a suitable and necessary period of time is allowed to exert its effect so that a satisfactory sterilization is obtained.
• the ozone formed has half-lives which are very dependent on its environment, i.e. the material in the vicinity of the 0 3 -molecules .
• the half-life depends on such parameters as the humidity of the air as well as the temperature and it can vary from about ten seconds to several days. A too rapid degradation in a closed container would result in that the required sterilizing dosage [f(time, concentration)] becomes too low.
• Example 1 Determination of the half-life for ozone.
• a 300 keV electron beam and an analyzer Ozomat MP Ozone (Anseros, Germany) were used.
• the ozone was generated with an acceleration voltage of 300 keV and a dosage of 20 kGy in sixty PET bottles which had been subjected to a small pressure above the atmospheric for the purpose of avoiding the penetration of air.
• the ozone concentrations in the bottles were then followed for 12.5 h.
• Bottles containing ozone generated in air were compared with bottles irradiated with electrons in an inert atmosphere.
• sealed PET bottles of 350 ml were tested by means of four different treatments: 1.
• the bottles contained air and were irradiated with an average dosage of 40 kGy; 3.
• the bottles contained nitrogen gas and were irradiated with an average dosage of 25 kGy;
• the bottles contained air and were not irradiated but treated as a reference example .
• Example 3 Examination of the lethal effect after ozone treatment .
• the effect of ozone in electron irradiated PET bottles was examined with reference to the number of killed microorganisms.
• Bacillus pumilus ATCC 27242 and Bacillus subtilis NCA 7252 were used as test organisms. The capacity of killing these organisms was determined as the logarithmic reduction which was defined as the number of organisms in a reference sample minus the number of surviving organisms.
• PET bottles were inoculated with one of the test organisms and exposed to an electron gun (10 eV, Ris ⁇ National Laboratories) with doses of 7 and 9 kGy, respectively, the bottles then being filled with 50 ml culture broth for each organism.
• the bottles were incubated and afterwards analyzed to assess whether any growth occurred in the bottles or not.
• the results in comparison with reference samples were statistically evaluated in a customary way (based on the method with "Most Probable Number") which is well known to the man skilled in the art.
• Fig. 1 shows the logarithmic reduction of B . pumilus and B . subtilis in helium and air (30 % relative humidity) with radiation dosages of 7 and 9 kGy, respectively, for the two microorganisms.
• the effects obtained by the sterilization according to the invention could be due to the following.
• this corresponds to about 10 9 electrons being passed through a microorganism during the sterilization process, and only a small part of these electrons will result in a directly lethal effect in the form of destruction of DNA.
• all the electrons pass through the cell membrane and will then generate membrane damages which weaken the organism and result in an increased probability of the ozone generated by the electron irradiation more easily being able to penetrate into the cell.
• the ozone can exert its additive effect.
• a supplementary effect can be explained by the two sterilization methods being able to act in different ways. The effect becomes synergistic in that the ozone destroys enzymes, and then above all in that the enzymatic DNA repair mechanisms are eliminated.
• the ability of the electrons to penetrate a package material is relatively low but depends of course on the radiation energy. Thanks to the invention the energy level required for electron irradiation is not influenced by the container locally having a large material thickness, such as for example the neck of a bottle. In that way energy levels less than 300 keV can be utilized, which results in that commercially available equipment can be utilized.
• An important advantage of the method according to invention is that the unfilled container used is manufactured closed and impervious. Thus, the generation as well as the degradation of the poisonous gas takes place inside an already pre-sealed container. When the container is subjected to electron irradiation a certain sterilization takes place and at the same time ozone is formed.
• the ozone Before the container is filled the ozone is allowed to act for such a long period of time that its action together with the initial effect of the electron irradiation results in a sufficient sterilization of the container. Since it takes much time to repair the injuries obtained from an electron irradiation it can be necessary to make use of a long storage time with ozone in the container.
• the container While the sterilization process still proceeds after the treatment of the container by means of electron irradi- ation the container is transported to the place of filling, where the container is filled and resealed in a sterile environment. If the time between the sterilization and the filling of the container is sufficiently long the ozone concentration will decrease. Consequently, the inconveni- ence of handling a poisonous gas is reduced when the container is filled. It is thus possible to let the degradation proceed to such a length that the ozone content is harmless when the container is opened in the filling machine .
• the ozone content can according to the invention also be adjusted by modifying the atmosphere within the container.
• the amount of ozone generated in the container can be increased by the addition of more oxygen to the container before it is sealed.
• the degradation rate of the ozone can be decreased by lowering the temperature in the container.
• an increased degradation rate is obtained when the temperature is increased. Any remaining residual ozone in a container can thus be eliminated by heating the container directly before the filling procedure.
• the degradation rate can also be increased by raising the humidity in the container.
• the humidity in the container By controlling the humidity in the container the water activity is also controlled, which in turn influences the death rate of the microorgan- isms during the sterilization process.

Landscapes

• Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Apparatus For Disinfection Or Sterilisation (AREA)
• Food Preservation Except Freezing, Refrigeration, And Drying (AREA)

Priority Applications (6)

Applications Claiming Priority (2)

Publications (1)

Family

ID=20404224

Family Applications (1)

Country Status (11)

Cited By (2)

Families Citing this family (18)

Citations (1)

Family Cites Families (3)

• 1996
  • 1996-10-14 SE SE9603736A patent/SE507526C2/sv unknown
• 1997
  • 1997-09-19 CN CN97198775A patent/CN1087258C/zh not_active Expired - Fee Related
  • 1997-09-19 EP EP97945128A patent/EP1023224B1/en not_active Expired - Lifetime
  • 1997-09-19 US US09/284,044 patent/US6355216B1/en not_active Expired - Fee Related
  • 1997-09-19 AT AT97945128T patent/ATE316039T1/de not_active IP Right Cessation
  • 1997-09-19 BR BR9711912A patent/BR9711912A/pt not_active Application Discontinuation
  • 1997-09-19 WO PCT/SE1997/001576 patent/WO1998016287A1/en active IP Right Grant
  • 1997-09-19 ES ES97945128T patent/ES2252796T3/es not_active Expired - Lifetime
  • 1997-09-19 JP JP10518240A patent/JP2001502278A/ja not_active Ceased
  • 1997-09-19 DE DE69735141T patent/DE69735141T2/de not_active Expired - Lifetime
  • 1997-09-19 AU AU46405/97A patent/AU4640597A/en not_active Abandoned

Patent Citations (1)

Also Published As

Similar Documents

Legal Events